1. Field of the Invention
The present invention relates to a novel recombinant Sabin type 1 poliovirus vector, in particular, to a recombinant Sabin type 1 poliovirus vector to induce the generation of neutralizing antibody, a vaccine composition comprising a recombinant poliovirus and a method for immunizing an individual against poliovirus.
2. Description of the Related Art
Recent standards for vaccine development commonly emphasize the mucosal immunity. Several researches for the development of effective mucosal vaccines have been performed as follows:
Firstly, cholera toxin or E. coli endotoxin have been suggested as a kind of mucosal immunogens (Munoz, E. et al., Cholera toxin discriminates between T helper 1 and 2 cells in T cell receptor-mediated activation: role of cAMP in T cell proliferation. J. Exp. Med. 1; 172(1):95–103(1990); Wilson, A. D. et al., Adjuvant action of cholera toxin and pertussis toxin in the induction of IgA antibody response to orally administered antigen. Vaccine 11(2):113–8(1993)). However, since cholera toxin and bacterial endotoxin may induce adverse effects in human, much more intensive studies are required for employing them as an adjuvant for mucosal vaccine developments.
Secondly, a microencapsulation technology in which antigens are encapsulated and administered has been reported (McGhee, J. R. et al., Isotype of anti-SIV responses in infected rhesus macaques and in animals immunized by mucosal routes. AIDS Res. Hum. Retroviruses 8(8):1389(1992); Marx., P. A. et al., Protection against vaginal SIV transmission with microencapsulated vaccine Science 28;260(5112):1323–7(1993)). However, this approach also has its own limitation to overcome for antigen combinations to achieve appropriate systemic and mucosal immunities.
Thirdly, viruses showing tropisms to the mucosal area via respiratory and digestive organs have been investigated as the most effective approach for induction of mucosal immunity, which are able to induce both cytotoxic T lymphocyte (CTL) and local mucosal immunity (Meitin C. A. et al., Influenza immunization: intranasal live vaccinia recombinant contrasted with parenteral inactivated vaccine Vaccine 9(10):751–6(1991); Offit, P. A. et al., Rotavirus-specific cytotoxic T lymphocyte response of mice after oral inoculation with candidate rotavirus vaccine strains RRV or WC3. J. Infect. Dis. 160(5):783–8(1989); London, S. D. et al., Intraepithelial lymphocytes contain virus-specific, MHC-restricted cytotoxic cell precursors after gut mucosal immunization with reovirus serotype 1/Lang. Reg. Immunol. 2(2):98–102(1989)).
Therefore, it was highly recommended to construct a viral vector with mucosal tissue-tropic viruses, resulting in the development of recombinant mucosal vaccines by integrating various viral subgenomes into the viral vector.
In this connection, much effort has been recently made to develop non-toxic viral vectors having higher potential for the induction of mucosal immunity. In particular, the development of vaccines using poliovirus has been extensively studied.
Studies for the development of poliovirus as a vector can be classified into 3 categories: (a) epitope substitution; (b) construction of defective minireplicon; and (c) autoprocessing recombinant vector (R. Andino, Science 265:1448–451(1994)); N. M. Mattion J. Virol. 68:3925–3933(1994); and Vaccine 95:293–297(1995)). In the third category, R. Andino et al. used wild type of poliovirus (type 1 Mahoney strain) and N. M. Mattion used type 3 Sabin for the development of viral vector, reporting their experimental results.
The approaches proposed by R. Andino and Mattion are considered the most promising. However, Sabin type 3 as well as Mahoney strain has its own limitation for the safety reasons mediated by back mutation.
Sabin developed poliovirus vaccine in 1963, which proliferates only in small intestine without neurotropism, and induces long-lasting mucosal immunity. It does not cause poliomyelitis even in the high titers. Among the Sabin strains, the Sabin 1 has been approved for its safety. During the last 40 years none of the case of vaccine-associated paralytic poliomyelitis (VAPP) has been reported in association with Sabin 1.
In these regards, the present inventors have developed recombinant live vaccine vectors by manipulating a genome of Sabin type 1, named “RPS-Vax” (see Korean Pat. Appln. No. 1997-37812). In addition, the present inventors have constructed Sabin type 1-based recombinant poliovirus vectors by inserting p24 gene of HIV-1, env gene of HIV-1 and core gene of HCV into the RPS-Vax vector system (see WO 99/7859).
The RPS-Vax-derived recombinant live vaccines are expected to take advantages of Sabin I vaccine strain, such as safety, oral administration, low cost and its mucosal immunogenicity.
Inactivated polio vaccine (IPV; Salk) was developed in 1953 as the first polio vaccine. The IPV was made of formalin-inactivated wild type polioviruses of types 1, 2 and 3. Recent inactivated polio vaccines, produced by culturing in human diploid cells or Vero cells, are much improved for their efficacy. They exhibit considerable preventive immunity even by twice inoculations. In addition, it has been suggested that theses vaccines could elicit the same seroconversion rate as that of oral polio vaccines (OPV) through thrice-basic inoculation. Although the IPVs are much more safe than oral live vaccines, they have some serious shortcomings: (a) demand of much higher does for immunization than live vaccines (1012 pfu/human vs. 5–10×105 pfu/human); (b) needle injection; (c) no held immunity; and (d) no musoal immunogenicity.
OPV has been one of the most successful vaccine programs during the last half of the 20th century. The incidence of poliomyelitis was sharply reduced by OPV development since 1963, and recently expected to be eradicated in the near future all over the world. The OPV has been produced in a form of cocktail comprising attenuated vaccine strains of Sabin types 1, 2 and 3. Recently, however, vaccine associated paralytic poliomyelitis (VAPP) has been reported in line with OPV vaccination in USA. Because of the VAPP by OPV, several developed countries, starting with USA and Germany since the year of 1999, have inclined to use IPVs rather than OPV.
Nevertheless, many underdeveloped countries still have lots of incidences of poliomyelitis in Southeast Asia and Africa. Even though very safe, IPV is not enough to keep these peoples from the poliomyelitis for its own limitations of weak immunogenicity, expenses and no capacity for mucosal immunity. Therefore, it is highly recommended to develop a safe and effective OPV to replace the conventional OPV.
Although several studies have been made for a long period of time to dispel the adverse effects associated with OPV, there has not yet been provided safe and effective vaccines for replacing conventional OPV vaccine.
Throughout this application, several patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications is incorporated into this application in order to more fully describe this invention and the state of the art to which this invention pertains.